tbuckley/cabot-search huggingface dataset:
Abstract 12671: Weight Loss Improves Cardiometabolic Health as Measured by Plasma Proteins in Individuals With Type 2 Diabetes
Authors: Naveed Sattar, Shahrad Taheri, Paul Welsh, David Astling, Jessica Chadwick, Michael Hinterberg, Emma Troth, Rachel Ostroff, Hadeel Zaghloul, Odette Chagoury, Roy Taylor, Michael Lean, Stephen A Williams
Journal: Circulation (2022)

Introduction: The DiRECT (UK cohort) and DIADEM-1 (Middle Eastern/North Africian cohort) trials in patients with type 2 diabetes demonstrated average weight loss of &gt;10kg spurred by dietary intervention led to 46-61% diabetes remission at 12 months. Here we investigated cardiometabolic outcomes of these cohorts using predictive proteomic SomaSignal ® tests. Methods: Eight cardiometabolic SomaSignal tests (each derived from ~5000 plasma proteins measurements using aptamer-based proteomics assay) related to cardiometabolic health were assessed in baseline and 1-year samples in intervention (DiRECT n=118, DIADEM-1 n=66) and control (DiRECT n=144, DIADEM-1 n=76) participants. Results: Despite differences in baseline characteristics (age, ethnicity, diabetes duration, cardiovascular (CV) risk factors), both intervention groups showed similar improvements in overall cardiometabolic outcomes (Figure). Seven SomaSignal tests in DiRECT and six SomaSignal tests in DIADEM-1 significantly improved in the intervention groups compared to respective control arms. Liver fat, glucose intolerance, body fat percentage, resting metabolic rate, visceral fat, and cardiorespiratory fitness predictions significantly improved in intervention arms of both trials with greater relative improvements seen in individuals that lost &gt;10kg. Additionally, CV risk improved significantly in the DiRECT intervention arm (which had higher baseline CV risk compared to DIADEM-1), as well as in both trials among individuals lost &gt;10kg. Conclusion: Proteomic changes suggest widespread improvement in cardiometabolic traits, including CV risk, across both trials of intentional weight loss in individuals with type 2 diabetes. Notably, greater relative improvements in all traits including CV risk were seen in individuals that lost &gt;10kg. These data suggest large intentional weight loss will improve future CV outcomes.
Abstract 12678: Steroids versus Steroid-Sparing Agents in Cardiac Sarcoidosis: A Retrospective Analysis of Clinical Outcomes
Authors: Angela Montes, Walter James, Jeremy R Burt, William Rieter, Richard Rissmiller, Jeffrey Winterfield, Jan Griffin, Brian Houston
Journal: Circulation (2022)

Introduction: Equipoise remains on whether initial therapy for cardiac sarcoidosis (CS) should consist of corticosteroids alone or include steroid-sparing agents (SSAs). This study retrospectively assessed outcomes of CS patients initially treated with prednisone only versus SSAs +/- prednisone. Hypothesis: We hypothesized that initial therapy inclusive of SSAs would be associated with reduced adverse outcomes. Method: We performed a retrospective review of CS patients seen at the MUSC Pearlstine Sarcoidosis Center of Excellence in the preceding year. The patients were divided into two cohorts: the prednisone group was defined as patients taking only prednisone for &gt; 3 months as initial therapy of CS. The SSA group was defined as patients taking SSAs (methotrexate or MMF) +/- prednisone within three months of initial therapy for CS. Cardiovascular outcomes after CS diagnosis were compared between the groups. Results: We included 107 patients for analysis (37 prednisone; 70 SSA (53% methotrexate, 47% MMF)). Patients in the SSA group were 77% less likely to develop heart failure with reduced ejection fraction (RR 0.23, p=0.0001), 72% less likely to develop heart failure with preserved ejection fraction (RR 0.28, p=0.001), 62% less likely to be hospitalized for heart failure (RR 0.38, p=0.02), 77% less likely to be hospitalized for ventricular tachycardia (RR 0.23, p=0.01), 60% less likely to develop ventricular arrhythmias (RR 0.4, p=0.003), 80% less likely to experience an ICD shock (RR 0.2, p=0.005), and 50% less likely to develop heart block requiring a pacemaker (RR 0.5, p=0.01) than the prednisone group (see Figure). Conclusions: In this study of CS patients, early therapy inclusive of SSAs was associated with significantly reduced heart failure and arrhythmia risks. Our study suggests that early therapy for CS should include SSAs. Future investigations in these cohorts will focus on between-group comparisons to assess for potential confounding factors.
Abstract 10075: Hematopoietic Mosaic Chromosomal Alterations and Cardiovascular Disease-Related Deaths Among Cancer Survivors: An Analysis of the UK Biobank
Authors: Maxine Sun, Marie-Christyne Cyr, Johanna Sandoval, Louis-Philippe Lemieux Perreault, Lambert Busque, Jean-Claude Tardif, Marie-Pierre Dube
Journal: Circulation (2022)

Introduction: Cancer survivors are at an increased risk for cardiovascular (CV)-related deaths. Recently, clonal hematopoiesis (CH) was described as a novel risk factor for both cancer and CV disease. However, the influence of CH on CV outcomes in cancer survivors has not been explored. Hypothesis: We hypothesized that CH captured by mosaic chromosomal alterations (mCA) could predict the risk of CV outcomes and death following cancer diagnosis. Methods: In the UK Biobank, we identified patients with a history of selected cancer types known for their high CV risk. mCAs were detected using DNA genotyping array intensity data. The association of mCA with CV-death, coronary artery disease (CAD)-death, and any cause death was performed using Cox proportional hazards regression, adjusting for age, sex, smoking, chemotherapy, radiotherapy, and ancestry. Exploratory analyses also included incident CV phenotypes. The specificity of the effect was assessed using a model with an interaction term between mCA and cancer history. Results: Among 48 919 unrelated individuals with a cancer diagnosis, 10 070 patients (20.6%) carried ≥1 mCA clone. Of those, 2432 were autosomal carriers and 1910 had a mCA in ≥10% of peripheral leukocytes. mCA prevalence increased with age: from 4.8% among those aged &lt;49 years old to 30.4% for those aged ≥70 years old. mCA was associated with an increased risk of CAD-death (HR 1.37, 95% CI 1.09-1.71, P= 0.006) and overall mortality (HR 1.07, 95% CI 1.02-1.11, P =0.006). In exploratory analyses, mCA was associated with higher risks of incident STEMI (HR 1.18, 95% CI 1.02-1.37, P =0.022) and peripheral vascular disease (HR 1.17, 95% CI 1.04-1.31, P =0.007). The effect of mCA was specific to cancer survivors for any cause of death ( P interaction &lt;0.001) but not for CAD-death ( P interaction =0.96). Conclusions: Our findings indicate that among cancer survivors, CH captured by mCA was associated with a higher risk of CAD death and overall mortality. Cancer survivors with CH may benefit from targeted CV screening and preventive measures to better manage individual CV risk.
Abstract 10531: Reactive Hyperemia Index and Coronary Plaque in Asymptomatic Adults - Insights From the Miami Heart Study at Baptist Health South Florida
Authors: Najah Khan, Shubham Lahan, Yaa Kwapong, Garima Sharma, Miguel Cainzos Achirica, Shozab S Ali, Lara Arias, Anshul Saxena, Ricardo C Cury, Matthew Budoff, Theodore Feldman, Michael J Blaha, Jonathan Fialkow, Khurram Nasir
Journal: Circulation (2022)

Objective: We aimed to evaluate the associations between the reactive hyperemia index (RHI), a non-invasive estimate of endothelial function, and coronary artery plaque presence and features on coronary computed tomography angiography (CCTA); and whether these associations differ by sex. Methods: Data from Miami Heart Study, an ongoing, prospective US cohort of individuals free of clinical ASCVD. A total of 2,097 participants underwent assessment of both RHI using EndoPAT® (abnormal RHI defined as &lt;1.67) and a CCTA scan. We computed the unadjusted prevalence of 4 plaque outcomes (any coronary plaque on CCTA, CAC score &gt;0, maximal coronary stenosis ≥50%, and presence of ≥1 high-risk plaque features) among individuals with and without abnormal RHI; overall and by sex. Multivariable logistic regression models were used to investigate the association between RHI and the outcomes adjusting for confounders, overall and by sex. Results: Of the 2,097 participants, mean age was 53 years, 50% were women, and 15% had abnormal RHI. Mean age was 54±7 vs. 53±7 years for normal vs. abnormal RHI, respectively, and 17% men vs 13% women had abnormal RHI. In unadjusted analyses, abnormal RHI was not associated with a significant higher prevalence of any of the study outcomes ( Figure Panel A ; all P &gt;0.05). Adjusting for sociodemographics, no statistically significant associations were observed between abnormal RHI and any of the coronary plaque features evaluated ( Panel B ). Similar observations were noted further adjusting for other risk factors. There was no evidence of interaction by sex in any of the associations (P for interaction: all &gt;0.05). Conclusions: In the Miami Heart Study, abnormal RHI measured using EndoPAT was not associated with coronary plaque in either women nor men. Our findings suggest that this measurement may be suboptimal in the assessment of endothelial function, and not informative in predicting the presence of subclinical coronary atherosclerosis.
Abstract 10951: Temporal and Global Trends of the Incidence of Sudden Cardiac Death in Hypertrophic Cardiomyopathy: A Meta-Analysis
Authors: Omar M Abdelfattah, Matthew W Martinez, Ahmed Sayed, Mohamed ElRefaei, Abdelrahman Abushouk, Ahmed Hassan, Ahmad Masri, Stephen L Winters, Samir R Kapadia, Barry J Maron, Ethan J Rowin, Martin Maron
Journal: Circulation (2022)

Introduction: Since hypertrophic cardiomyopathy(HCM) initial description, sudden cardiac death (SCD) has been the most feared complication of HCM. Hypothesis: Temporal, geographical, and age-related trends of SCD rates in HCM have drastically decreased over time. Methods: Databases were systematically searched to Nov 2021 for studies reporting on SCD event rates in HCM. Patients with SCD equivalents (appropriate ICD shocks and non-fatal SCD) were excluded. Random-effects model was utilized to pool study estimates calculating the overall incidence rates(IR) for each time-era, geographical region, and age-group. We analyzed 2 eras (before vs. after 2000, following implementation of ICD in HCM). Following 2000, 5-year intervals were used to reflect the temporal change in SCD. Results: 98 studies (N=70,510patients and 431,407patient-years) met inclusion criteria. Overall rate of HCM SCD was 0.43%/year (95% CI: 0.37-0.50%; I 2 =75%; SCD events:1,938; person-years of follow-up: 408,715), with young patients(&lt;18 years) demonstrating a&gt;2-fold-risk for SCD vs. adults(18-60years) (IR:1.09%; 95% CI: 0.69-1.73% vs. IR: 0.43%; 95% CI: 0.37-0.50%)(P-value for subgroup differences:&lt;0.01). Contemporary SCD rates from 2015-present were 0.32%/year; significantly lower compared to 2000 or earlier (IR: 0.32%; 95% CI:0.20-0.52%, vs. IR: 0.73%; 95% CI:0.53-1.02%,respectively). Reported HCM-SCD rates were lowest in North America (IR: 0.28%;95% CI:0.18-0.43%) and highest in Asia(IR: 0.67%; 95% CI:0.54-0.84%). Conclusions: Contemporary HCM-related SCD are low (0.32%/year) representing a 2-fold decrease compared to prior treatment eras, with young HCM patients at the highest risk. SCD risk stratification maturation and primary prevention ICD application are likely responsible for the notable decline in SCD trends. Moreover, worldwide geographical disparities in SCD was evident, underscoring the need to increase access to SCD prevention for all HCM patients.
Abstract 11852: Impact of Heart Failure on New Cancer Diagnosis and Cancer Mortality in Patients With Ischemic Heart Disease Who Underwent Percutaneous Coronary Intervention
Authors: Yuya Sakuma, Takeshi Shimizu, Yuta Kurosawa, Himika Ohara, Yuki Muto, Yu Sato, Takatoyo Kiko, Akihiko Sato, Tomofumi Misaka, Akiomi Yoshihisa, Takayoshi Yamaki, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2022)

Background: Recently, it has been reported that heart failure may be associated with high risk for development of cancer. However, this theory is not definitive and more epidemiological data are needed. Here we investigated the impact of heart failure on the incidence of new cancer diagnosis and cancer mortality in patients with ischemic heart disease who underwent percutaneous coronary intervention (PCI). Methods and Results: Consecutive 1787 patients with ischemic heart disease who underwent PCI were enrolled. Patients were divided into two groups according to the presence or absence of heart failure, and followed up for incidence of new cancer diagnosis and mortality due to cancer. Patients with heart failure (n = 434) were older (73.4 vs. 68.0 years, P &amp;lt; 0.001) and had higher prevalence of comorbidities such as anemia (63.2 vs. 40.2%, P &amp;lt; 0.001), chronic kidney disease (61.4 vs. 40.3%, P &amp;lt; 0.001), atrial fibrillation (20.7 vs. 14.0%, P = 0.001) and stroke (21.8 vs. 15.8%, P = 0.004) than those without heart failure (n = 1353). The percentage of smokers did not differ between two groups (P = 0.374). During follow up period (mean of 1528 days), there were 142 new cancer diagnoses and 60 cancer deaths. Of 142 new cancers, gastrointestinal cancer was the leading site (39.4%), followed by lung cancer (14.1%), prostate cancer (11.3%), liver or biliary tract cancer (10.6%), hematologic cancer (9.9%) and others. The incidence of new cancer diagnosis and cancer mortality were significantly higher in patients with heart failure than in those without heart failure (P &amp;lt; 0.001 and P = 0.001, respectively). In the multivariate analyses after adjusting for confounding factors including smoking, heart failure was an independent predictor of new cancer diagnosis and cancer death (hazard ratio 2.22, P &amp;lt; 0.001 and hazard ratio 1.78, P = 0.036, respectively). Conclusion: Heart failure was associated with incidence of new cancer and cancer death in patient with ischemic heart disease.
Abstract 11827: A Case of Rapidly Progressive Aortic Valve Stenosis Secondary to Chronic Hypercalcemia
Authors: Maan Kathryn L Gozun, Mohammed Ali, Todd Nagamine, Limpruttidham Nath, Kuo Alan
Journal: Circulation (2022)

Introduction: Moderate hypercalcemia may be well-tolerated, but rapid calcium deposition to the aortic valve may have life-threatening consequences. Clinical case: We present a case of a 77-year-old female with a history of retroperitoneal liposarcoma complicated by hypercalcemia. The patient had had recurrent hypercalcemia for the past 6 months, ranging from 12-14 mg/dL. She complained of 4 weeks of progressive dyspnea and orthopnea. Physical exam showed jugular venous distension and bilateral pitting edema. A transthoracic echocardiogram (TTE) showed critical aortic stenosis (AS) with a valve area of 0.4 cm2, peak velocity of 6 m/s, and a mean gradient of 90 mmHg (Figure 1). Her last TTE just 9 months prior showed mildly thickened aortic valve leaflets without evidence of stenosis with a valve area of 2.2 cm2, peak velocity of 1.4 m/s, and mean gradient of 4 mmHg (Figure 2). Discussion: The most common cause of AS is age-related calcification. However, the role of hypercalcemia in AS has not been well-defined. Typically, the valve area is expected to decline by 0.1cm2 per year. Surprisingly, our patient’s valve area decreased from 2.2 cm2 to 0.4 cm2 in just 9 months. Rapid decline is usually associated with typical cardiovascular risk factors, however, studies have begun to recognize hypercalcemia as a potential risk factor for rapid progression. In our case, we believe our patient suffered from rapidly progressive AS secondary to chronic hypercalcemia due to malignancy. Conclusions: The severity of AS should be closely monitored in hypercalcemia and further studies are warranted to develop strategies for secondary prevention.
Abstract 11836: Lack of Engagement in Physical Activity Predicts All-Cause of Mortality and Rehospitalization in Patients With Heart Failure
Authors: Geunyeong Cha, Misook L Chung, Terry A Lennie, Chin-Yen Lin, Martha J Biddle, Jiarong R Wu, Debra K Moser
Journal: Circulation (2022)

Background: Lack of physical activity is associated with a higher risk of mortality and rehospitalization for patients with heart failure (HF). Although exercise is recommended to patients with HF to optimize health, engagement in physical activity (EPA) remains poor due to many barriers. There is limited knowledge about whether EPA is a unique predictor of event-free survival. Purpose: The purpose of this study was to determine whether EPA was an independent predictor of event-free survival in patients with HF controlling for demographic, clinical factors, and depressive symptoms. Method: We included 1135 patients with HF who completed a survey of EPA (Medical Outcomes Study Specific Adherence Scale [MOS-SAS]), depressive symptoms (Patient Health Questionnaire-9), and demographic and clinical characteristics (age, sex, smoking status, body mass index, and NYHA class). They were followed for 2-years. Event-free survival was the composite endpoint of time to all-cause hospitalization or death. Patients were categorized into EPA (stated engaged in physical activity at least once a week) and non-EPA (stated did not engage in physical activity at all) groups using an activity item of the MOS-SAS. Cox regression analysis was used to determine if EPA was an independent predictor of event-free survival. Result: Among patients (mean age = 64 ± 12.7 years, 64% male, 83% white, 44% NYHA class III/IV), 65% engaged in physical activity, while 35% did not. During follow-up, 118 deaths and 385 rehospitalizations occurred. Patients in the non-EPA group were 1.3 times more likely to die or be hospitalized compared with patients in the EPA group (HR =1.255, 95% CI: 1.039 - 1.517). Conclusion: We found that EPA, even at a low level (at least once a week) was beneficial in reducing the risk of mortality and hospitalization events. Innovative interventions should be developed to motivate non-EPA patients to engage in physical activity.
Abstract 12670: The End-of-Life Experience of Pediatric Vad Patients: A Report From the Action Registry
Authors: Seth A Hollander, Kimberly Pyke-Grimm, Muhammad F Shezad, Farhan Zafar, Melissa Cousino, Chris Feudtner, Danton Char
Journal: Circulation (2022)

Introduction: Although most pediatric VAD patients survive to transplantation, some die on device therapy. The end-of-life experience of pediatric VAD patients is not well characterized. Hypothesis: Invasive interventions are common in pediatric VAD patients at the end-of-life. Methods: Retrospective review of pediatric VAD patients in the ACTION registry who died on device therapy between 3/2012-9/2021. Demographic and clinical data, including invasive interventions used at the end-of-life and the location of death, were analyzed. Results: 107/721 (15%) of patients died on device at a median age of 5 years (IQR:1, 16) at 43 days (IQR: 17, 91) post implant. Goals of VAD therapy were bridge to candidacy for 50 patients (51%), bridge to transplant for 44 (37.6%), destination therapy for 2 (1.7%). The most common cause of death was multi-organ failure (n=35, 30%), followed by infection (n=12, 10.3%). Eighty-five of 92 patients (92.4%) died with a functioning device in place. Most patients were receiving invasive interventions (mechanical ventilation, 75%; vasoactive infusions, 62%) at the end-of-life. ( Table 1 ). Only 10 (9%) patients died at home. Utilizing these data, we identified and estimated the frequency of four common end-of-life trajectories for pediatric VAD patients. (Figure 1). Conclusions: Aggressive interventions are common at the end-of-life of pediatric patients with VADs. Dying at home is uncommon. Identification of common end-of-life patterns will serve as an outcome measure and inform future practices to promote informed patient and provider decision-making to reduce suffering in those who die on device support.
Abstract 10715: Therapeutic Efficacy of Drpitor1a, a Novel Dynamin-Related Protein 1 (DRP1) Inhibitor, in Preclinical Pulmonary Arterial Hypertension
Authors: Danchen Wu, Ross D Jansen-van Vuuren, Asish Das Gupta, Kuang-Huieh Chen, Ruaa Al-Qazazi, Ashley Martin, Nolan M Breault, Jeffrey D Mewburn, Patricia D Lima, Oliver Jones, Stephen L Archer
Journal: Circulation (2022)

Introduction: Dynamin-related protein 1 (DRP1) is a large GTPase that mediates mitotic fission (the division of mitochondria which is coordinated with mitosis, ensuring equitable distribution of mitochondria to daughter cells). In pulmonary arterial hypertension (PAH) pulmonary artery smooth muscle cells (PASMC), mitotic fission, and DRP1 activity are increased, contributing to its hyperproliferative phenotype. We investigated the therapeutic efficacy of Drpitor1a, a novel, small molecule, Drp1 GTPase inhibitor, in a rat PAH model. Methods: A single dose of monocrotaline (MCT, 60mg/kg, SC) or PBS was injected to female Sprague-Dawley rats on day 0 (n=20 for MCT and n=15 for PBS). On day 14, the development of PAH was confirmed by echocardiography and the rats were randomized for treatments. An indwelling catheter was implanted through the left jugular vein on day 15. Drpitor1a (1mg/kg) or normal saline (NS) was administered by IV every 48 hours from day 17 to day 27. Right ventricular (RV) structure and function were assessed on day 28 with echocardiography. Pulmonary hemodynamics was evaluated on day 29 using right heart catheterization (RHC). Results: MCT rats developed PAH with RV dysfunction on day 14. There was no statistical difference between the Drpitor1a and NS groups at randomization. At the endpoint, MCT+Drpitor1a rats, vs. MCT+NS rats, had a significantly reduced severity of pulmonary hypertension evident as longer pulmonary artery acceleration time (PAAT) and lower pulmonary vascular resistance index. Drpitor1a also improved RV function, evident as greater RV free wall thickening (RVFWT%), increased tricuspid annular plane systolic excursion (TAPSE), and increased cardiac index (CI). Drpitor1a regressed pulmonary artery medial thickening and inhibited RV hypertrophy without hepatological, renal or hepatic toxicities. Conclusion: Drpitor1a is a safe and effective treatment for preclinical PAH.